CD44

Chr 11

CD44 molecule (IN blood group)

Also known as: CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL, HUTCH-1, HUTCH-I

NCBI Gene: 960 ENSG00000026508 UniProt: P16070 OMIM: 107269

CD44 encodes a cell-surface glycoprotein that serves as a receptor for hyaluronic acid and functions in cell-cell interactions, cell adhesion, and migration by assembling signaling complexes that coordinate cytoskeletal reorganization. Mutations in CD44 are associated with blood group Indian system variants, which typically represent benign polymorphisms rather than disease-causing mutations. The gene shows low constraint to loss-of-function variants (pLI near zero), suggesting haploinsufficiency is unlikely to cause severe developmental phenotypes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Blood group, Indian system]MIM #609027

Active trials

2423

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CD44

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.000

Z-score 3.25

OE 0.45 (0.31–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.84Z-score

OE missense 0.88 (0.81–0.96)

358 obs / 405.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.31–0.66)

0≤0.351.4

Missense OE?0.88 (0.81–0.96)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 18 / 40.2Missense obs/exp: 358 / 405.7Syn Z: -0.03

Background carrier burden — how many people carry a rare variant somewhere in CD44?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

967 rare PASS variants

Rare truncating (LoF)

1 in 830

109 rare PASS variants

Rare synonymous (reference)

1 in 150

301 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD44. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,300
South Asian	~43k	1 in 54	1 in 1,200
Remaining (unassigned)	~30k	1 in 61	1 in 680
European (Finnish)	~27k	1 in 120	1 in 760
Admixed American	~22k	1 in 58	1 in 430
African / African American	~21k	1 in 55	1 in 840
East Asian	~20k	1 in 65	1 in 1,100
Ashkenazi Jewish	~13k	1 in 360	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 62	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 18 coding exons well covered in gnomAD exomes; exons 4, 13, 15 marginal. Genomes: all 18.? see exons ↓